CXCR4 and SDF1 are part of the core regulatory mechanism regulating migration of muscle precursor cells to the developing limb

Abstract

The ligand CXCR4 and its receptor SDF1 have been associated on several occacions with the formation of the limb musculature, specifically SDF1/CXCR4 signaling has been implicated to be associated with migration of the limb muscle precursor cells. In this thesis I will provide an overview of SDF1/CXCR4 signaling and how this pleiotropic signaling cascade could be involved in the regulation of the core mechanism regulation migration of limb muscle precursor cells. These interactions point to a top role of FGFs, SF/HGF and Shh in the limb bud mesenchyme to control both CXCR4 and SDF1 signaling, either directly (SDF1, CXCR4) or potentially through other factors such as NF-kB. Downstream of CXCR4 three potentially interesting mechanism can be distinguished. First JAK/STAT signaling which is also controlled by EphA4 which is also expressed in the migrating muscle precursors. Second a positive feedback loop of CXCR4 involving SHIP2, PI-3K and NF-kB. Third we can distinguish a potential mechanism by which CXCR4 regulates c-met by signaling through MAPK and Gab1.